Piroxicam (4-hydroxy-2-methyl-N-2-pyridyl-2H-1, 2-benzothiazine-3-carboxamide-1, 1-dioxide), a substance belonging to the group of oxicams (dihydrothiazine derivatives) has been known for many years as a non-steroidal antirheumatic agent/antiphlogistic agent (NSAR) and analgesic, e.g. for injuries and tooth extractions (see DE-PS 1943265). In spite of its high efficacy and long-duration effect, its oral application is however accompanied by the side-effects of NSAR, such as gastrointestinal haemorrhage, damage to the heart and kidney function (see e.g. "Pharmazie in unserer Zeit 13 (1984) 177, 185).
In order to avoid or reduce side effects, it is therefore desirable to supplement the oral application by a topical application, especially in the case of localized injuries or diseases of the locomotive system.
For a topical application, i.e. administration on and through the skin over a longer period of time, medicinal plasters were proposed which contain an antiphlogistic agent as an effective substance (see DE-A-3344691, 3347277, 3347278).
EP-A-0331382 describes compositions for transdermal application having an increased transdermal flow, which contain besides the effective substance, e.g. piroxicam, and an aqueous solvent system, a penetration-enhancing agent from the group of the 1-alkyl azacycloheptane-2-ones.
From the Japanese published patent application JP 5913714 (8413714), piroxicam-containing anti-inflammatory and analgesic compositions are known, e.g. in the form of an ointment with an oil in water (O/W) ointment base, which contains carboxyvinyl polymer, ethanol, propylene-glycol, diethanolamine, 2-hydroxyethyl cellulose ether, polyvinyl pyrrolidone and water.
EP-B-0101178 describes a topical, antiphlogistic drug in the form of a gel-ointment in an aqueous system, which contains an effective, antiphlogistic amount of piroxicam, 10 to 50% by wt. of a lower alkanol, a gel-forming amount of carboxyvinyl polymer, 5 to 40% by weight of a multivalent alcohol and an amount rendering piroxicam soluble of at least one alkanol amine in water.
Such formulations of non-steroidal antirheumatic agents, such as e.g. piroxicam, for the topical application in hydrophilic bases, such as e.g. the above-named oil-in-water gel- ointment form, or gels which contain the piroxicam in propylene glycol, ethyl- and isopropyl alcohol, have the advantage that as systems dilutable with water they can be easily washed off; moreover they have no smell and are non-greasy.
Piroxicam forms a monohydrate with lemon-yellow color. This hydrate is less soluble than piroxicam, so that aqueous solutions of piroxicam in the pH-range of about 2-8 are to be regarded as metastable in the respect that yellow piroxicam monohydrate can crystallize out of them. The known formulations containing piroxicam in hydrophilic bases, such as e.g. O/W creams suitable for topical application, therefore have the disadvantage that upon a longer storage time, on account of the property of piroxicam to convert into the yellow monohydrate, they turn yellow. On account of this instability, and also on account of the unattractive optical appearance caused by the discoloring, these formulations are frequently rejected by the consumer.
EP- A- 0179430 describes a piroxicam-containing preparation, in which the yellow piroxicam monohydrate is incorporated in an O/W cream.
Formulations in hydrophilic bases generally have the characteristic that the effective substance is administered well to the skin.
The formulations on the basis of hydrophilic bases for topical use, such as gels or O/W creams, have the disadvantage, however, that they lead to a desiccation of the skin.